Inflammation occurs in response to tissue injury or infection. The acute inflammatory response is marked by fever, increased vascular permeability, alterations in plasma metal and steroid concentrations and leukocytosis. Associated with the leukocytosis and localization of the leukocytes to the injured or affected tissue is the release of a barrage of proteolytic enzymes of various specificities which degrade affected tissue and/or invading organisms. Control of acute inflammation must be regulated by the body to prevent hyperaccumulation of inflammation-causing agents and thereby avoid degradation of healthy tissue. One pathway of control is the stimulation of liver cells, i.e. hepatocytes, to produce a series of plasma proteins known collectively as acute phase proteins. The acute phase proteins include antiproteases which inactivate proteolytic enzymes released at the site of injury, clotting and complement components, opsonins and carrier proteins along with others of unknown function. The acute phase proteins include .alpha.1 acid glycoprotein, .alpha.1 proteinase inhibitor (.alpha.1 antitrypsin), .alpha.1 antichymotrypsin, haptoglobin, hemopexin and fibrinogen in most species along with C-reactive protein, C3 and Factor B complement components and serum amyloid A protein in man and in addition .alpha. 2 macroglobulin and .alpha.1 cysteine proteinase inhibitor (major acute phase protein) in the rat.
Some medical conditions are due to an abundance of inflammatory mediators and proteins. Septacemia, or acute pancreatitis, for example, may result in an excess of proteolytic enzymes being released and marked tissue destruction. Conditions such as this may be due to an inadequate release of acute phase proteins to limit inflammation. On the other hand, post-surgery recovery in some patients is associated with infection and poor wound healing which may be due to an inadequate inflammatory response or an excessive anti-inflammatory response. Accordingly, it is possible that once the identity of the liver stimulant is known therapies designed to compensate for its absence or malfunction can remedy such conditions as septacemia and related conditions.